Nuclear Features Research Articles

Risk stratification of cytologically indeterminate thyroid nodules with nondiagnostic or benign cytology on repeat FNA: Implications for molecular testing and surveillance.

Evidence guiding the management of cytologically indeterminate thyroid nodules with nondiagnostic (ND) or benign cytology on repeat fine-needle aspiration (FNA) is limited. This study evaluates the utility of molecular testing and estimates the risk of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and cancer among such nodules. This was a retrospective single-institution review of thyroid nodules from adults that were classified as atypia of undetermined significance (AUS) or follicular neoplasm (FN) on initial FNA and underwent repeat FNA for cytology and Afirma testing (June 2013-July 2021). The association between repeat FNA cytology and RNA yield for Afirma was determined. Histologic outcomes were integrated with Afirma results to define end points for each nodule. A total of 691 AUS and FN nodules underwent repeat FNA and Afirma testing. Diagnostic Afirma results were obtained in 98% of cases overall and in 91% of nodules with ND cytology on repeat FNA. Using combined molecular and histologic end points, the NIFTP and/or cancer prevalence for nodules with ND cytology on repeat FNA was 9% (95% confidence interval [CI], 0.042-0.182), falling between those nodules classified as benign (5%; 95% CI, 0.029-0.094) and those classified as AUS or FN (18%; 95% CI, 0.140-0.218) on repeat FNA, although not reaching statistical significance from either subgroup (p=.38 and .10, respectively). AUS and FN nodules that are ND on repeat FNA have low but nonnegligible risk of NIFTP and/or cancer and may benefit from molecular testing, given the low test failure rate in this subgroup. Conversely, AUS and FN nodules reclassified as benign on repeat FNA have a very low risk of NIFTP and/or cancer and are unlikely to benefit from molecular testing.

Multichannel experimental and theoretical approach to the C12(O18,F18)B12 single-charge-exchange reaction at 275 MeV: Initial-state interaction and single-particle properties of nuclear wave functions

Background: Single-charge-exchange reactions are appropriate tools to study the nuclear response to one-particle/one-hole isospin probes, gaining additional interest from the connection to beta decay. This analogy has been recently extended to second order, connecting double-charge-exchange reactions and double beta decays. Nowadays, the availability of powerful experimental setups and advanced nuclear theories and models allows one to access precious information on key nuclear structure aspects embedded in the widely sought neutrinoless double beta decay. Purpose: We intend to bring to light the main nuclear structure and reaction features involved in the O18+C12 collision at 275 MeV incident energy. In this paper, the main focus is on the role of the initial- and final-state interactions in the overall reaction dynamics and on the single-particle nuclear structure properties accessed via the study of single-nucleon transfer reactions. Forthcoming articles will be devoted to go into the details of the response to one- and two-particle/hole isospin probes. Methods: Cross-section energy spectra and angular distributions were measured in a unique experimental setup for the C12(O18,O18)C12 elastic and inelastic scattering, the C12(O18,O17)C13 one-neutron stripping, the C12(O18,F19)B11 one-proton pickup, and the C12(O18,F18)B12 single-charge-exchange nuclear reactions. A unique comprehensive and coherent theoretical calculation, able to describe the whole network of direct reactions using state-of-the-art nuclear structure and reaction theories, was performed, and it is presented for the first time in this article. This holistic approach, applied both to the experimental and theoretical analysis, is the main feature and worth of the work here presented. Results: The energy and angular resolutions achieved in each reaction channel allowed us to isolate specific transitions and to map the diffraction patterns in the angular distributions. The cross-section calculations describe well the experimental data, both in terms of the absolute values and diffraction patterns. Although the distorted wave Born approximation (DWBA) calculations prove to be accurate in describing all the studied channels, better results are achieved when the couplings to inelastic transitions in both the incoming and outgoing partitions are introduced, as done in the coupled channels Born approximation (CCBA) calculations. Otherwise, no real improvement is found when the coupling effects among different partitions are explicitly taken into account in the coupled reaction channels (CRC) calculations. Conclusions: The multichannel approach proposed in this paper is a promising method for accurate investigations of direct reactions originating in heavy-ion collisions. This is quite appealing for the precise spectroscopy of heavy nuclei proposed in many areas of nuclear physics. An example is the NUMEN project with its challenging commitment to provide valuable information on neutrinoless double beta decay nuclear matrix elements from single- and double-charge-exchange cross-section measurements.1 MoreReceived 18 July 2022Accepted 23 January 2023DOI:https://doi.org/10.1103/PhysRevC.107.024605©2023 American Physical SocietyPhysics Subject Headings (PhySH)Research AreasCharge-exchange reactionsCollective modelsDirect reactionsNuclear many-body theoryOptical, coupled-channel & distorted wave modelsShell modelSpectroscopic factors & electromagnetic momentsTransfer reactionsProperties6 ≤ A ≤ 19TechniquesNuclear data analysis & compilationNuclear reactionsSpectrometers & spectroscopic techniquesNuclear Physics

MicroRNA expression profiling of RAS-mutant thyroid tumors with follicular architecture: microRNA signatures to discriminate benign from malignant lesions

PurposeRAS mutations represent common driver alterations in thyroid cancer. They can be found in benign, low-risk and malignant thyroid tumors with follicular architecture, which are often diagnosed as indeterminate nodules on preoperative cytology. Therefore, the detection of RAS mutations in preoperative setting has a suboptimal predictive value for malignancy. In this study, we investigated differentially expressed microRNA (miRNA) in benign and malignant thyroid tumors with follicular architecture carrying mutations in RAS genes.MethodsTotal RNA was purified from 60 RAS-mutant follicular-patterned thyroid tumors, including follicular adenoma (FA), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), papillary and follicular thyroid carcinoma cases (PTC, FTC); 22 RAS-negative FAs were used as controls. The expression analysis of 798 miRNAs was performed by digital counting (nCounter nanoString platform).ResultsComparing RAS-mutant and RAS-negative FAs, 12 miRNAs showed significant deregulation, which was likely related to the oncogenic effects of RAS mutations. Twenty-two miRNAs were differentially expressed in RAS-mutant benign versus malignant tumors. Considering the tumor type, 24 miRNAs were deregulated in PTC, 19 in NIFTP, and seven in FTC and compared to FA group; among these, miR-146b-5p, miR-144-3p, and miR-451a showed consistent deregulation in all the comparisons with the highest fold change.ConclusionsThe miRNA expression analysis of follicular-patterned thyroid tumors demonstrated that RAS mutations influences miRNA profile in benign tumors. In addition, several miRNAs showed a histotype-specific deregulation and could discriminate between RAS-mutant benign and RAS-mutant malignant thyroid lesions, thus deserving further investigation as potential diagnostic markers.

Investigating human chromosome organization by whole-genome simulations.

Both theoreticians and experimentalists have been dedicating significant effort to studying chromosome organization and its relation to gene expression and regulation. Many experimental procedures were designed, such as Hi-C or ChIA-PET, to capture structural information of chromosomes. Several theoretical models were proposed to understand the principles underlying chromosome compartmentalization. MiChroM is a model that describes the compartmentalization behavior of interphase chromosomes. Compared to experimental data, the agreement of the in silico contact maps suggested that phase separation of A/B compartments is a key feature determining the structure of individual chromosomes. In this work, we use the Open-MiChroM software to simulate the 46 chromosomes of a GM12878 human cell at 50 kb resolution, seeking to understand whether the nuclear organization of the whole genome would rely on the same principles observed for the organization of a single chromosome. The ensemble of structures generated by our simulations captures chromosome organization within territories and phase separation of chromatin compartments. Inside a chromosome territory, active chromatin localizes preferentially in the periphery, while inactive chromatin lies on the inside. The intra-chromosomal contact maps and the shape metrics of each territory are consistent with experimental data. The resulting genome architecture resembles the inverted nucleus configuration, with active chromatin towards the periphery. In the interface between chromosomes, we also observe phase separation of compartments. However, the inter-chromosomal maps present higher contact probabilities for heterochromatin loci when compared to the experimental data. These results suggest that the interactions of chromatin with other nuclear features like the lamina greatly influences inter-chromosomal interactions while also affecting the overall positioning of chromosomes in the nucleus.

Spatially Resolved Molecular Approaches for the Characterisation of Non-Invasive Follicular Tumours with Papillary-like Features (NIFTPs).

Noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) are low-risk thyroid lesions most often characterised by RAS-type mutations. The histological diagnosis may be challenging, and even immunohistochemistry and molecular approaches have not yet provided conclusive solutions. This study characterises a set of NIFTPs by Matrix-Assisted Laser Desorption/Ionisation (MALDI)-Mass Spectrometry Imaging (MSI) to highlight the proteomic signatures capable of overcoming histological challenges. Archived formalin-fixed paraffin-embedded samples from 10 NIFTPs (n = 6 RAS-mutated and n = 4 RAS-wild type) were trypsin-digested and analysed by MALDI-MSI, comparing their profiles to normal tissue and synchronous benign nodules. This allowed the definition of a four-peptide signature able to distinguish RAS-mutant from wild-type cases, the latter showing proteomic similarities to hyperplastic nodules. Moreover, among the differentially expressed signals, Peptidylprolyl Isomerase A (PPIA, 1505.8 m/z), which has already demonstrated a role in the development of cancer, was found overexpressed in NIFTP RAS-mutated nodules compared to wild-type lesions. These results underlined that high-throughput proteomic approaches may add a further level of biological comprehension for NIFTPs. In the future, thanks to the powerful single-cell detail achieved by new instruments, the complementary NGS-MALDI imaging sequence might be the correct methodological approach to confirm that the current NIFTP definition encompasses heterogeneous lesions that must be further characterised.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear feature: clinical, pathological, and molecular update 5 years after the nomenclature revision.

The term non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was proposed in 2016 and incorporated as a new entity in the World Health Organization (WHO) classification of tumours of endocrine organs in 2017. Since then, there has been debate regarding the histological criteria for the diagnosis, the need for molecular studies or the risk of lymph node metastasis or recurrence associated with this entity. Over the years, the concept of NIFTP evolved, now including both small (<1 cm) and large (>4 cm) tumours and oncocytic lesions. On the other hand, recent data on NIFTP in the setting of thyroid follicular nodular disease or frequent coexistence of malignant tumours raised concerns regarding the follow-up of these patients. Today, both pathologists and clinicians still face several challenges in the diagnosis, treatment, and follow-up of patients with NIFTP.

Predicting recurrence in osteosarcoma via a quantitative histological image classifier derived from tumour nuclear morphological features

AbstractRecurrence is the key factor affecting the prognosis of osteosarcoma. Currently, there is a lack of clinically useful tools to predict osteosarcoma recurrence. The application of pathological images for artificial intelligence‐assisted accurate prediction of tumour outcomes is increasing. Thus, the present study constructed a quantitative histological image classifier with tumour nuclear features to predict osteosarcoma outcomes using haematoxylin and eosin (H&amp;E)‐stained whole‐slide images (WSIs) from 150 osteosarcoma patients. We first segmented eight distinct tissues in osteosarcoma H&amp;E‐stained WSIs, with an average accuracy of 90.63% on the testing set. The tumour areas were automatically and accurately acquired, facilitating the tumour cell nuclear feature extraction process. Based on six selected tumour nuclear features, we developed an osteosarcoma histological image classifier (OSHIC) to predict the recurrence and survival of osteosarcoma following standard treatment. The quantitative OSHIC derived from tumour nuclear features independently predicted the recurrence and survival of osteosarcoma patients, thereby contributing to precision oncology. Moreover, we developed a fully automated workflow to extract quantitative image features, evaluate the diagnostic values of feature sets and build classifiers to predict osteosarcoma outcomes. Thus, the present study provides a novel tool for predicting osteosarcoma outcomes, which has a broad application prospect in clinical practice.

Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features: What a Surgeon Should Know.

The inclusion of the less aggressive follicular form of papillary thyroid cancer (PTC) is associated with an increase in the incidence of the condition, with the follicular variant of PTC being the most common of all variants. The majority of individuals with the encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) are treated as though they have classic thyroid cancer, despite the availability of mounting evidence to contradict the aforementioned. According to numerous research, a certain type of noninvasive-EFVPTC (NI-EFVPTC) demonstrated poor histopathologic diagnostic reproducibility and has received aggressive treatment similar to that of a classical thyroid neoplasm. Therefore, to replace the term NI-EFVPC, a new nomenclature for these tumors, called "noninvasive follicular thyroid neoplasm with papillary-like nuclear characteristics" (NIFTP), was introduced in the year 2016. The present paper explores this recently introduced terminology, clinical, histologic, and molecular features, and diagnostic criteria.

Follicular carcinoma originating from struma ovarii: A case report

Follicular carcinoma originating from struma ovarii is a clinically rare low-grade malignant tumor. The pathological diagnosis of ovarian thyroid follicular carcinoma is predominantly based on the infiltrative growth and vascular involvement of tumor cell nests of different sizes in the ovarian parenchyma. Here we present a case of this malignancy in which the bilateral ovaries, right oviduct wall, myometrial surface, omentum, and bladder reflex were extensively involved Microscopically, the thyroid follicles in this case showed infiltrative growth of nodules of different sizes in the ovarian stroma. The epithelial layer of the follicles was atypical, but with no nuclear features of papillary thyroid carcinoma such as nuclear groove and nuclear pseudoinclusions. Immunohistochemistry showed positive expression of thyroglobulin, thyroid transcription factor-1, and cytokeratin19, with a Ki-67 index of 5% +. Immunohistochemical results combined with microscopic morphology allowed a diagnosis of follicular carcinoma originating from struma ovarii. After exclusion of contraindications to surgery, the patient underwent surgical exploration on July 26, 2022, during which frozen pathological examination was performed. The patient recovered well and was discharged. At the first follow-up visit in October 2022, the patient had an excellent survival. The analysis of the microscopic morphological characteristics and immunohistochemistry deepened our understanding of the pathological characteristics of ovarian and thyroid follicular carcinoma, and further provides a diagnostic reference for other clinicians who will encounter these conditions in the future.

Cytological Features of "Non-Invasive Follicular Tumour with Papillary like Nuclear Features" - A Single Institutional Experience in India.

The term noninvasive follicular tumor with papillary-like nuclear features (NIFTP) was introduced as a surrogate for noninvasive encapsulated follicular variant of papillary thyroid carcinoma with a defined set of histopathologic criteria. There are very few studies depicting the cytological cues for the diagnosis of NIFTP. The objective of the study was to determine the spectrum of cytological features in fine needle aspiration cytology (FNAC) smears of cases histopathologically diagnosed as NIFTP. This was a retrospective cross-sectional study conducted over a duration of four years between January 2017 and December 2020. All surgically resected cases (n-21), who met the diagnostic criteria of NIFTP on histopathology and who underwent preoperative FNAC were included and reviewed in the study. Out of a total of 21 cases, at FNAC, diagnosis of benign, suspicious for malignancy, follicular variant of papillary thyroid carcinoma, and classic papillary thyroid carcinoma (PTC) was rendered in 14 (66.6%), 2 (9.5%), 2 (9.5%), and 3 (14.28%), respectively. Scanty cellularity was noted in 12 (57.1%) cases. Papillae, sheets, and microfollicles were seen in 1 (4.7%), 10 (47.6%), and 13 (61.9%) cases, respectively. Nucleomegaly, nuclear membrane irregularities, nuclear crowding, and overlapping were seen in 7 (33.3%), 9 (42.8%), and 9 (42.8%), respectively. Nucleoli, nuclear grooving, and inclusions were seen in 3 (14.2%) 10 (47.6%), and 5 (23.8%) cases, respectively. At FNAC, NIFTP can be found in every category of The Bethesda System for Reporting Thyroid cytopathology (TBSRTC). Nuclear membrane irregularities, nuclear grooving, mild nuclear crowding, and overlapping were noted in a modest number of cases. However, the absence or rare occurrence of features such as papillae, inclusions, nucleoli, and metaplastic cytoplasm may help prevent an overdiagnosis of malignancy.

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Pitfalls of Cytological and Histopathologic Diagnosis

Classical papillary thyroid carcinoma (PTC) is the commonest primary thyroid neoplasm. Besides PTC, significant histological variants that differ from classical PTC in regard to the morphological, cytologic and histologic features are mentioned; among them is follicular variant papillary thyroid carcinoma (FVPTC). The update WHO classification and the update Bethesda system reclassified FVPTC introduced a new entity which is "non-invasive follicular thyroid neoplasm with papillary like nuclear features" (NIFTP) that is characterized by an indolent behavior with encapsulated noninvasive growth features. Recently this entity is considering one of an indeterminate cytological categories (category III-IV-V). Update studies are found a combination of triple diagnostic procedures included sonographical, cytologic and molecular investigations can be suspecting preoperative diagnosis. Methods: A total of 150 selected cases of solitary thyroid nodules (STNs) with preoperative FNAC have an indeterminate follicular patterned cytological lesions with their underlying thyroidectomies that were collected in a 5-year period included in this article. Results: Majority of our cases were females and suffering from neck swelling. Cytollogically all the enrolled cases were lying in the indeterminate categories and histologically they were encapsulated with variable sizes follicles, nuclear features, no vascular invasion, no psammoma bodies, no tumor necrosis or mitosis. Also, there is no any extra-thyroid invasion. Conclusion: The accurate diagnosis of this entity “”NIFTP” carries many congratulations in regard that is “not malignant” category among both update TBSRTC and the final histopathological examination of the excised thyroid tissue.

Clinico-Pathological Spectrum of Alveolar Soft Part Sarcoma: Case Series from a Tertiary Care Cancer Referral Centre in India with a Focus on Unusual Clinical and Histological Features.

Alveolar soft part sarcoma (ASPS) is characterized by distinctive histomorphology of variably discohesive epithelioid cells arranged in nests and translocation of t(x;17) (p11.2;q25) resulting in ASPSCR1-TFE3 fusion. The aim of the present study is to review the clinical, histopathological, and immunohistochemical profile of ASPS with a focus on unusual histological features. The present study is retrospective and descriptive. All cases with a diagnosis of ASPS were retrieved with clinical and radiology details. 22 patients of ASPS were identified. The most common site was the lower extremity and the size range was 3-22 cm. 54.5% of the patients had metastasis, with the lung as the most common site. Metastasis preceded detection of primary tumour in two cases. All cases showed similar histopathology of monomorphic epithelioid cells arranged in nests encircled by sinusoidal vasculature. Architecturally, the organoid pattern (81.8%) was followed by the alveolar pattern. 68.2% of the cases showed apple bite nuclei as the predominant nuclear feature. Rare nuclear features included binucleation (n=13), multinucleation (n=8), pleomorphism (n=4), nuclear grooves in three cases and intranuclear inclusion in one case, mitosis (n=5), and focal necrosis (n=6). All cases were positive for TFE3 and negative for AE1/AE3, EMA, HMB45, PAX8, MyoD1, SMA, synaptophysin, and chromogranin. Only two cases showed focal S100 positivity while one showed focal desmin positivity. Diffuse strong nuclear TFE3 positivity is sensitive for ASPS in an appropriate clinicoradiological context. Due to the high propensity for early metastasis, complete metastatic work-up and long term follow up is recommended.

What is the contribution of tumor capsule thickness and tumor nucleus diameter to differential diagnosis in encapsulated variant thyroid papillary carcinomas?

Objective: Capsule thickness and papillary carcinoma nuclear features are common diagnostic criteria for invasive follicular variant papillary thyroid carcinoma (IEFVPTC), non-invasive follicular thyroid neoplasm with papillary nuclear features (NIFT-P), and encapsulated papillary thyroid carcinoma (E-PTC). Our goal in this study is to evaluate these two histomorphological criteria using computerized image analysis systems and to determine whether they can serve as auxiliary criteria for distinguishing these diagnostic groups. Materials and methods: 10 patients were selected from IEFVPTC, NIFT-P, and E-PTC diagnostic groups. Slides containing the largest tumor diameter were scanned and digitized. Using computerized image analysis systems, tumor capsule thickness was measured from 4 areas of 4 equal quadrants, and the average tumor capsule thickness (TCT) was determined. Furthermore, from these 4 equal quadrants, the nucleus diameter of 10 clearly distinguishable cells was measured to determine the average tumor cell nucleus diameter (ND). Results: TCT and ND histomorphological criteria were statistically significant among the diagnostic groups. For IFVPTC diagnosis, both TCT and ND were found to be significant diagnostic tools. We demonstrated that ND can easily be used as a diagnostic tool for NIFT-P, whereas more caution is required for TCT. Conclusion: Differentiating papillary nuclear feature-containing follicular variant thyroid papillary carcinomas is challenging. In this study with a limited number of patients, we demonstrated that the TCT and ND criteria can, to some extent, contribute to differential diagnosis between diagnostic groups. Future studies with larger patient groups and more advanced computerized image analysis programs will yield more promising results.

Behavior of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) During Initial Follow up

Behavior of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) During Initial Follow up

Collecting Duct Carcinoma of the Kidney

Purpose: Collecting duct carcinoma of the kidney (CDC) is an aggressive subtype of renal cell carcinoma with a dismal prognosis. The available knowledge concerning optimal management is still unclear. We report the largest single-institutional experience in the management of CDC. Materials and Methods: All the cases of CDC which were diagnosed at our center following a radical or partial nephrectomy in the past 15 years were included. Treatment details, radiological features, and histological features were reviewed. Descriptive statistics were used to show the clinicopathological profile and management of these patients, and Kaplan–Meier overall survival (OS) estimate was calculated. Results: Eighteen patients who were diagnosed and underwent the primary intervention at our center were included. The median age of patients was 40 years, with a male-to-female ratio of 5:1. Typical histopathological features included high-grade nuclear features, stromal desmoplasia, and tubular architecture. Surgery was the primary modality of treatment. Five (28%) patients who had metastases received adjuvant therapy, three received interferon-alpha therapy, and two received adjuvant chemotherapy with gemcitabine and cisplatin. The median follow-up was 19 months (range: 3–46 months). Kaplan–Meier OS estimate was 68% at 1 year and 48% at 3 years. Conclusion: CDC of the kidney often presents at an advanced stage, and has a poor prognosis. Survival remains poor despite surgery and adjuvant therapy.

Evaluation of Nuclear Morphometry and Ki-67 Proliferative Marker in Astrocytomas: A Ambispective Study

Introduction: Astrocytomas are the commonest primary Central Nervous System (CNS) tumours. Its diagnosis is based on histopathological criteria defined by the World Health Organization (WHO) 2016 that grades astrocytoma into four grades. The subjective nature of WHO grading has prompted for more objective methods to evaluate nuclear features. Furthermore, Ki-67, a marker of cellular proliferation is a useful diagnostic tool that also helps in prognostic evaluation and to plan adjuvant therapy in astrocytomas. Aim: To evaluate the nuclear morphometry and Ki-67 proliferative marker in astrocytomas and to assess the relationship of WHO grade with proliferative activity using Ki-67 immunostaining. Materials and Methods: This ambispective study was conducted in the Department of Pathology, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India, with a total duration of four years (October 2017 to September 2021). From 35 astrocytoma cases, Haematoxylin and Eosin (H&amp;E) stained slides were retrieved and reviewed appropriately by two pathologists and graded using the WHO criteria. Nuclear morphometric analysis was performed on the H&amp;E slides using Olympus BX-41 research microscope. The parameters evaluated were mean nuclear length, mean nuclear diameter, mean nuclear perimeter, mean nuclear area, Mean Nuclear Roundness Factor (MNRF) and mean nuclear ellipse form. The cases were then stained with Ki-67 antibody. The relationships between WHO grade of astrocytoma and nuclear morphometry and WHO grade with proliferative index was analysed. Results: According to WHO grading, four cases were Grade 1 (11.4%), 12 grade 2 (34.3%), six grade 3 (17.1%) and 13 grade 4 (37.1%). Significant correlation was seen between WHO grading and mean nuclear length, diameter, perimeter, area and Ki-67 with p-value of less than 0.001. Conclusion: Astrocytoma is an extremely heterogeneous disease with unpredictable outcome. The widely used WHO grading is subjective, while nuclear morphometry, using computer assisted image analysis, can ensure more objective assessment. The Ki-67 index could provide valuable information and may compliment the other parameters.

MASC Gets UNMASKED: Visiting a Rare Tumor with Emphasis on Cytomorphological Features.

Secretory carcinoma (SC) is a newly described entity which has been often misdiagnosed earlier as acinic cell carcinoma on cytology. Diagnosing SC was initially based upon identifying the ETV6:NTRK3 fusion gene with the help of fluorescence in situ hybridization (FISH). Lately, with more knowledge of the reliable histomorphology, cytology, and immunohistochemistry features, definitive diagnosis can be confidently made without the help of FISH in almost every case. Six histologically confirmed cases of SC were studied. The cytology slides of all the six cases were retrieved and reviewed to identify the characteristic features which could have helped in raising the possibility of SC on fine needle aspiration cytology itself. Cell blocks were also studied, wherever available. Patients were all male with average age of 35.2 years. The six cases in the current study demonstrated at least focal cytoplasmic vacuolization of varying sizes, papillae formations, and bland nuclear features on fine needle aspirate smears. It was also seen that S-100 and mammaglobin immunohistochemistry (IHC) are very helpful in confirming the diagnosis. The results of the current study highlight the cytomorphological features which may help in clinching the diagnosis SC on cytology itself. They also highlight certain cytological features which help to rule out the other differential diagnoses.

Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (Bethesda Category - III) in Thyroid Cytology

Introduction: Fine-needle aspiration (FNA) cytology is a reliable method to diagnose thyroid lesions. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is universally followed for thyroid cytology reporting. Out of the six categories described, Category III, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is the most heterogeneous one. Materials and Methods: In this study conducted in a tertiary health care center in Eastern India over 2 ½-year period, 868 thyroid FNAs were performed and the cytology smears were interpreted using the TBSRTC. There were 32 FNAs in Category III. Histopathology report was available in nine cases. Results: The risk of malignancy (ROM) considering noninvasive follicular thyroid carcinoma with papillary nuclear features (NIFTP) as benign was 9.3% and by considering NIFTP as malignant was 21.8%. Conclusion: The ROM for AUS/FLUS in our study was within the revised ROM criteria. In Category III, surgery is preferable in nodules which harbor suspicious features either clinically or according to ultrasound findings.

Challenges in Risk Stratification of Solid Atypical Mixed Echogenicity Thyroid Nodules.

Background: To determine the prevalence and risk of malignancy (ROM) in solid atypical mixed echogenicity thyroid nodules (SAMENs) with sonographic patterns not classifiable by the 2015 American Thyroid Association Ultrasound Risk Stratification System (NC ATA). Methods: We searched our prospectively collected endocrine surgery thyroid nodule (TN) database, with particular attention to those solid nodules that were NC ATA. An algorithm assigned each into one of the five ATA risk groups per the 2015 American Thyroid Association Ultrasound Risk Stratification System (ATA USRSS). TNs that the algorithm could not assign to a risk group were deemed NC ATA and were subsequently analyzed. Additionally, we categorized this group using an algorithm based on the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). We were specifically interested in the characteristics that resulted in non-classification by the 2015 ATA USRSS and the fine needle aspiration biopsy (FNAB) cytology and surgical pathology results from the group. Results: We evaluated data from 5,040 nodules, of which 1,772 had surgical pathology. There were 150 solid nodules not classified by 2015 ATA USRSS, all of which demonstrated atypical features along with iso-, hetero-, hyper-and mixed echogenicity (solid atypical mixed echogenicity nodules-SAMENs). Sixty of these nodules were excised and sent for surgical pathology, while 90 were followed without surgical excision. Out of the 90 that did not undergo surgery, 82 underwent FNAB with cytologic evaluation. Of our 150 SAMENs, 40 were malignant by surgical histology and six were likely malignant by cytology (total SAMEN ROM without noninvasive follicular thyroid neoplasm with papillary-l ike nuclear features 31%). The most common sonographic pattern present in our SAMEN group consisted of an isoechoic solid component with microcalcifications (28/40-70% of all excised malignant nodules). In our excised malignant SAMENs, 50% demonstrated follicular-patterned neoplastic architecture while 48% displayed papillary architecture. Conclusion: Our study demonstrates that SAMENs with at least one suspicious sonographic feature: including (1) microcalcifications; (2) irregular or other suspicious margins,;opulation, and a higher ROM (31%) than the intermediate-risk group of the 2015 ATA USRSS (10-20%).

Is it Possible to Diagnose "Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features" Preoperatively?

There is no accepted consensus or algorithm for the preoperative diagnosis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in patients with thyroid nodules. In this study, we evaluated the importance of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in the differential diagnosis of NIFTP. Pathology preparations of 209 patients with a follicular variant of papillary thyroid carcinoma (FVPTC) diagnosed after thyroid surgery in a tertiary health center between January 2010 and January 2020 were re-evaluated. Patients were divided into NIFTP and encapsulated follicular variant papillary thyroid carcinoma (EFVPTC) to compare. Of the patients, 58 (27.7%) were NIFTP, and 151 (72.3%) were EFVPTC. There was no statistically significant difference in terms of age (p = 0.46), tumor size (p = 0.51), gender (p = 0.48), and surgical technique (p = 0.78) between the groups. The probability of the neutrophil-to-lymphocyte ratio (NLR) > 2 is more common in the EFVPTC group. It was statistically significant that the NIFTP group was 1.96 times more likely to have NLR > 2 (OR: 1.96, 95% CI: 1.06-3.63) (p < 0.05). However, there was no risk difference between the groups in terms of the platelet-to-lymphocyte ratio (PLR) (OR: 0.76, 95% CI: 0.41-1.43) (p > 0.05). The diagnosis of NIFTP should be kept in mind in the evaluation of patients whose thyroid fine-needle aspiration (FNA) biopsy results are in the intermediate group. NIFTP exhibits better prognostic findings than classic thyroid papillary cancer and EFVPTC. Therefore, preoperative diagnosis of NIFTP in line with laboratory, ultrasonography, and FNA findings will save the patient from unnecessary overtreatment.